NSU-MD Faculty Articles

Title

Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA.

ISBN or ISSN

0022-1767

Publication Title

Journal of immunology

Volume

166

Issue

5

Publication Date / Copyright Date

3-1-2001

First Page

2953

Last Page

2960

Publisher

American Association of Immunologists

Abstract

Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape.

Disciplines

Medicine and Health Sciences

Keywords

Adjuvants, Immunologic, Cells, Cultured, Clone Cells, Cross Reactions, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, Dendritic Cells, Dissection, Epitopes, T-Lymphocyte, Gene Amplification, Humans, Lymphocyte Activation, Male, Prostate-Specific Antigen, Prostatic Neoplasms, RNA, Messenger, RNA, Neoplasm, T-Lymphocytes, Cytotoxic, Transcription, Genetic, Transfection

Peer Reviewed

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